Institute for Radio Engineering and Electronics of the Russian
Academy of Sciences, Moscow, Russia

Institute for Higher Nerve Activity and Neurophysiology of the
Russian Academy of Sciences, Moscow, Russia

1. Introduction

Electromagnetic millimeter (MM) waves ( = 1 to 10 mm) correspond
to the extremely-high-frequency (EHF) band: f = 300 to 30 GHz. In
the electromagnetic spectrum, this band lies between the
super-high-frequency (microwave) band and the optical (infrared)
band.

The first wideband oscillator with an electric tuning of
oscillation frequency was developed and brought into lot production
in the U.S.S.R. under the leadership of Academician N. D. Devyatkov
and Professor M. B. Golant in the mid 1960s. The oscillator was
called an O-type backward-wave tube. It was employed both to
improve radio navigation systems and to create new communications
systems

[1, 2].

In those days, scientists all over the world discussed possible
application of electromagnetic waves in nontraditional fieldssuch
as biology, medicine, and some others. Creators of the MM-wave
oscillator suggested an idea of investigating biological effects of
MM-wave radiation. These waves were of special interest for
scientists because they were unlikely to take part in phylogenesis
of terrestrial beings. The point is that MM-wave radiation is
virtually absent in natural conditions. This is due to its strong
absorption by the Earth’s atmosphere: MM waves are absorbed eagerly
by water vapor.

It was hypothesized that low-intensity (nonthermal) MM waves might
have a nonspecific effect on biological structures and organisms.
Foreground investigations, which have been performed in the
U.S.S.R. and then in Russia for 30 years, made it possible to
enunciate a hypothesis that vital functions in cells are governed
by coherent electromagnetic EHF waves: the alternating
electromagnetic field of these waves maintains interaction between
adjacent cells to interrelate and control intercellular processes
in the entire being. This hypothesis formed the basis for a new
scientific lead that was originated at the turn of several branches
of sciences: biophysics, radio electronics, medicine, and some
others. This lead was thereafter named millimeter
electromagnetobiology.

2. Fundamental Results of Experimental
Investigations of the Effect of Low-intensity Millimeter Waves on
Biological Objects

Early experimental studies were carried out at the All-Union
Cancer Research Center of the U.S.S.R. Academy of Medical Sciences.
This center is among leading medical establishments in Russia.
Investigations made on microorganisms (bacteria E. coli) and
laboratory animals (mice and rats) discovered an interesting
experimental fact. It was found that different microorganisms
exposed to MM-wave radiation exhibited a frequency-dependent
biological effect [3]. The equivalent intrinsic Q-factor
(calculated from the formula Q = f0/f0.5, where f0 is the
resonance frequency and f0.5 is the FWHM of the biological effect)
amounted to hundreds and thousands of units. The mechanism of
appearance of such great values is unexplained so far.

Another essential and accepted fact is that a biological effect
plotted against the electromagnetic-wave power exhibits a
“plateau.” Experiments made on microorganisms demonstrated that the
plateau could extend for three orders of magnitude, or more [4, 5].
It was also found that a threshold intensity that gave rise to
biological effects could be as small as units or tens of microwatts
per square centimeter.

Hence, the very first experimental investigations established that
MM waves can bring about biological effects at low radiation
powersat low-intensity or nonthermal powers. In this case, the
integral heating of an exposed surface does not exceed a
physiologically significant temperature increment, which amounts to
approximately 0.1C. The effect of MM waves on living beings was
called informational. This was done from analogy with communication
lines, which reveal the same behavior. A. S. Presman was the first
to introduce the term informational to electromagnetobiology[6].

By now, scientists have amassed a great experimental and
theoretical material about the effect of low-intensity MM-wave
radiation on biological objects [79]. Below, we shall outline the
most essential facts.

 EHF radiation is strongly absorbed by water and aqueous
solutions of organic and inorganic substances [10]. When
electromagnetic radiation is absorbed by water, its wave energy is
converted into rotational, translational, and librational degrees
of freedom. For example, a 1-mm thick water layer attenuates
MM-wave radiation by 20 dB at  = 8 mm and by 40 dB at  = 2 mm[10]. This fact is of great importance for biology: suffice it to
say that all biological organisms contain much water. For example,
the human skin contains more than 65% water. Hence, almost all
radiation is absorbed at a skin depth of 0.5 to 1 mm (the epidermis
and the top dermis). When MM waves are incident on the skin, they
are primarily targeted at its anatomical structures, such as
receptors, capillaries, cells, liquid (aqueous) solutions of
organic and inorganic substances [11].

 MM-wave absorption violates the additivity law of a solvent
(water) and solutes [12]. For a particular solution, real
absorption can be greater or smaller than the additive one.
Absorption depends on the intermolecular interaction between a
solvent and a solute. When an aqueous solution shows poor
absorption, this may indicate, for example, that part of water
molecules is in a bound state. As a result, absorption decreases
because water molecules lose their rotational degrees of freedom[13].

An excess of real absorption over the additive one can arise from
the “heating” of separate molecules or molecular groups due to the
appearance of additional degrees of freedom (mainly, the rotational
ones).

– MM waves stimulate production of biologically active substances
by immunocompetent cells. This phenomenon is carefully discussed in[14] and was additionally proven in other studies. Indirectly, it
is confirmed by the polytherapeutic effect of EHF therapy and by
the enhanced nonspecific resistivity of an organism.

– EHF radiation changes microbial metabolism. This fact was
observed in almost all experimental investigations on microbes. MM
waves were reported to have a pronounced effect on the microbial
vital activity. After MM-wave exposure, microorganisms began to
produce biologically active substances. Now, this phenomenon is
used in various biotechnological processes [15].

– MM-wave radiation stimulates ATP (adenosine 5 -triphosphate)
synthesis in green-leaf cells. For the first time, the effect of
radiation on ATP synthesis was observed in leaves of the indoor
plant Balsaminus [16]. As is known, ATP is a universal chemical
source of energy in living cells. The fact that MM waves stimulate
ATP synthesis has an effect on microbial vital activity. This
phenomenon was indirectly confirmed in medical practice (when a
diseased being revealed normalization of vital processes) and in
experimental studies (when an organism enhanced the synthesis of
biologically active substances).

– EHF radiation increases crop capacity (for example, after
presowing seed treatment). The first observations in this field
were apparently made by the authors of [17]. Experiments were made
on various indoor plants. It was reported [18] that MM waves have a
stimulating effect both on the germination of popular garden seeds
and on their crop capacity. A number of other investigations
obtained similar results for seeds of other plants and trees.

– MM waves change the rheological properties of blood capillaries.
Experimental studies revealed that dielectric capillaries (which
simulate capillaries in tissues) exhibited resonance absorption of
MM waves. The equivalent Q-factor of resonance peaks was found to
was found to be tremendously highon the order of 103 to 104. Note,
it is rather hard to force metal cavities to yield such Q-factors
in the microwave and MM-wave bands. The resonance absorption in
water and in various aqueous solutions is accompanied by a
considerable decrease in the adhesive force between the inner
capillary wall and the flowing fluid [19]. However, the mechanism
of this phenomenon is still unexplained. Nevertheless, the
“capillary” effect can explain the efficiency of MM-wave-based
treatment of obliterating endarteritis.

– EHF radiation excites CNS (central nervous system) receptors and
induces bioelectric responses in the cerebral cortex. It is natural
to question how information is transmitted from a thin skin layer
to the internal organs. The fact that the human CNS is involved in
the realization of MM-wave-induced effects is discussed in [2022].
It was demonstrated that 80% of healthy people can reliably
perceive low-intensity MM waves (sensory indication). However, such
perception exhibits sensory asymmetry. Peripheral application of MM
waves was shown to have an effect on the spatiotemporal
organization of brain biopotentials. As a result, the cerebral
cortex develops a nonspecific activation reaction (tonus
enhancement). According to [2022], pain receptors (nociceptors)
and mechanoreceptors are the CNS receptors that perceive MM waves.
MM-wave-induced effects are realized mainly by the nonspecific
somatosensory system, which is linked to almost all regions of the
brain.

– Even a single MM-wave exposure is memorized (“water memory”).
The last several years have seen publications of new findings about
the role of water and aqueous solutions in the realization of
biological mechanisms of MM waves. For the first time, a hypothesis
about an important role of water was advanced in 1979 in [23]. New
properties of water exposed to MM waves are described in [24, 25].
The authors of [24] discussed the excitation of metastable states
in the energy diagram of water structure. It was shown that the
physical mechanism of “water memory” formation is associated with
the network of hydrogen bonds. In a hydrogen bond between two water
molecules, a hydrogen atom that is located between two oxygen atoms
has two equiprobable positions. This atom (proton) can be regarded
as a particle tunneling between two potential wells. The possible
tunneling splits the proton energy level into two closely spaced
levels with an energy difference of Ep. In this case, the proton
tunneling frequency is given by p = Ep/h, where h is Planck’s
constant. The tunneling frequencies of clusters and clathrates
{(H2O)n, where n = 50 to 60} fall within the millimeter and
submillimeter bands. As a result, these systems absorb MM waves in
a resonant manner. Experimental investigations described in [25]
showed that water (aqueous solutions) can store information
(“memory”) about MM-wave irradiation for a long timefrom a few
minutes to several tens of minutes). This information manifests
itself in the retention of biological (biochemical) activity by
water after irradiation termination.

 Water and aqueous solution bleach as a result of the SPYo
effect•. Sensational are the results of experimental and
theoretical investigations that showed the feasible existence of
“low-loss transmission windows” in water and water-containing
objects (we mentioned about it earlier). These windows were
observed at the intrinsic resonance frequencies of water clusters[2628]. This phenomenon occurs in a narrow range of exposure
poweron the order of fractions and units of microwatts.

 MM waves induce convective motion in the bulk and thin layers of
fluid. MM waves may give rise to compound convective motion in the
intracellular and intercellular fluid. This lifts restrictions from
diffusive motion of fluid near cells. As a result, the
transmembrane mass transfer and charge transport become more
active. Model experiments confirmed this statement. Convection is
readily observed at a power density of 0.5 to 1 mW cm2. The
results of such experiments are described in [29, 30]. Note,
convection may occur not only in the bulk of fluid but also in thin
layers whose depth is less than 1 mm. This phenomenon can be
observed at threshold powers of incident radiationon the order of
several microwatts [30].

 EHF radiation increases the hydration of protein molecules. It
is known that dehydration of protein molecules affects them. As a
result, proteins go from a functionally active to functionally
passive state [12]. It was demonstrated by experiment that MM waves
can restore the hydration number. Experiments unfinished by Yu. I.
Khurgin were a cause for such a statement. They were made using
chymotrypsin. It served as a catalyst for a biochemical reaction.
Chymotrypsin catalytic reactivity was varied by changing its
hydration number: when the hydration number decreased, the reaction
yield also decreased. It was observed that MM-wave irradiation
increased the reaction yield. This could result solely from an
increase in chymotrypsin hydration, which enhanced protein
activity. The hydration number increased because of electromagnetic
energy conversion into the rotational-translational energy of water
molecules. This changed the “protein-water” complex from a
functionally passive to functionally active state.

 MM waves give a microthermal massage. It was demonstrated by
experiment that MM waves produce a nonuniform distribution on the
skin surface. Experiments were carried out using the “Yav’1″
device having a rectangular horn. When exposed to MM-wave
radiation, the skin surface exhibited several thermal extrema,
which were visualized by a thermal imager. Although the average
temperature rise was insignificant, two or three maxima were
overheated by several degrees of centigrade. In a thermal image,
the extrema looked like points”thermal spikes.” When the EHF
carrier was modulated in frequency or amplitude, the spikes were
found to migrate across the skin surface. The author of [31]
suggested that this effect could give a thermal massage to the skin
receptors (by analogy with conventional thermal acupuncture).

 EHF radiation excites acousto-electric oscillations (the
Frohlich oscillations) in plasma membranes. A theoretical study[32] showed that plasma membranes may generate coherent
oscillations, which are sustained by metabolism. These oscillations
occur either in the entire plasma membrane or in its separate
parts. In the electromagnetic spectrum, these oscillations fall
within the EHF band. The authors of [33] believe that such
oscillations are nothing else but acousto-electric oscillations.
The purpose of these oscillations is to stimulate the transport of
water and other substances across the membrane, sustaining it in
the active state. Later on, some authors who tackled the problem of
EHF therapy expressed another interesting view. An illness deranges
the intrinsic oscillations of the membrane, whereas an EHF therapy
device simulates the dying oscillations of the membrane. As a
result, EHF radiation restores the oscillations, normalizes
membrane functioning, and cures the sick person.

3. Experimental Clinical Investigations

L. A. Sevast’yanova was among the first scientists who launched
investigations into the biological effects of low-intensity MM
waves on mammals (1969-1971) [34-36]. She demonstrated that
preliminary MM-wave irradiation may counteract X-ray-induced
effects in the bone marrow [3741]. She also estimated MM-wave
penetration into the skin of animals. L. A. Sevast’yanova
determined the distribution pattern of MM-wave power for some
animals and human beings. The estimated penetration depth showed
that MM waves produce a mediate protective effect.

Investigations that lasted for more than 20 years were performed
on more than 12,000 laboratory animals (mice and rats). The
response of the hematogenous system was evaluated by the count and
state of marrow cells (karyocytes) present in the right and left
femoral arteries as well as in the spleen. The results obtained are
given below.

 The biological effect depends on the power flux density. The
biological effect has one feature observed in vivo and in vitro.
This is a threshold dependence of the biological effect on the
power flux density. It was found that an excess of the power flux
density above the threshold value produces no changes in the
biological effect.

 The biological effect depends on the wavelength. Experiments
were made on laboratory animals which were sequentially exposed to
MM waves and X rays. When MM-wave irradiation was performed at
wavelengths of 7.07 mm, 7.10 mm, 7.12 mm, 7.15 mm, 7.17 mm, 7.20
mm, 7. 22 mm, 7.25 mm, and 7.27 mm, karyocytes constituted 85% to
90% of the control values. However, when MM-wave irradiation was
performed at wavelengths of 7.08 mm, 7.09 mm, 7.11 mm, 7.13 mm,
7.14 mm, 7.16 mm, 7.18 mm, 7.19 mm, 7.21 mm, 7.23 mm, 7.24 mm, and
7.26 mm, karyocytes made up 50% to 60% of the control values. This
karyocyte count corresponded to that obtained for X-ray exposure
alone.

 The biological effect depends on the MM-wave exposure site
location. The damage degree of karyocytes decreased when the
occiput and the hip were exposed to MM waves at wavelengths of 7.10
mm and 7.12 mm. However, this degree remained unchained when
irradiation was performed at wavelengths of 7.11 mm and 7.13 mm.
Similar resultsbut at different wavelengthswere obtained for
other bodily regions of animals, such as the flank, head, abdomen,
and brachium. For example, the damage degree of karyocytes
decreased at wavelengths of 7.11 mm and 7.13 mm, whereas it
remained unchanged at wavelengths of 7.10 mm and 7.12 mm. Hence,
some particular wavelength produces a biological effect in each
bodily region.

 The biological effect depends on the MM-wave exposure area. The
combination of X rays with overall and local MM-wave irradiation
produced similar biological effects. The latter consisted of
decreasing the X-ray-induced damage degree of karyocytes. It was
found that MM waves took effect even if the exposure area was as
small as 10 mm2. However, when MM waves were not modulated in
frequency, the effect was unstable. Conversely, when they were
modulated in frequency, the effect was stable.

As far back as the 1970s, W. R. Adey advanced a hypothesis that
the electromagnetic spectrum should contain “amplitude-frequency
windows” in which biological effects are more pronounced [42]. The
above-described results served as the first experimental
verification of this hypothesis. It was inferred that biological
effects of electromagnetic radiation, and particularly of MM-wave
radiation, are determined by its biotropic parameters, such as the
intensity, frequency, signal waveform, location, exposure,
etc.

It is known that cells exposed to X rays reveal different types of
lesions that depend on the X-ray dose. These lesions manifest
themselves in the form of chromosome aberrations, decreased mitotic
activity, and inhibited reproductive ability. In turn, this leads
to reduced karyocyte and blood-cell counts.

Most radioprotectors do not exhibit sufficient selectivity. As the
radiation dose increases, they themselves may produce toxic
effects. Results obtained by L. A. Sevast’yanova were evidence that
MM waves have a protective effect and that they influence
karyocytes selectively.

When MM-wave irradiation was followed by X-ray exposure, intact
animals (without grafts) revealed a smaller damage degree of
karyocytes as compared to those exposed to X rays alone: by the
fifth day, the karyocyte deficiency was 15% only, whereas it
amounted to 38% in animals exposed sequentially to X rays and MM
waves.

Like radiation, antineoplastic compounds isolate the DNA-membrane
complex and retard the DNA and RNA synthesis. At the cellular
level, the effect of X-ray exposure has much in common with the
effect of chemotherapy compounds: a sluggish cellular cycle,
delayed mitosis, chromosome aberrations, as well as reproductive
and interphase death.

Investigations were made of the combined influence of MM waves and
antineoplastic compounds. They demonstrated that MM-wave radiation
with some particular parameters can counteract the detrimental
effect of antineoplastic compounds on the hematogenous system.
Furthermore, MM waves were found to stimulate the functional
activity of stem cells.

Speaking about hematogenous system responses, the combined
influence always yielded more karyocytes than X rays or
antineoplastic compounds alone. This held true for all combinations
used in the experiments. Being combined with antineoplastic
compounds, both single and multiple MM-wave exposures produced a
decrease in the damage degree of karyocytes. MM-wave irradiation
alone produced no changes in the hematogenous system of
animals.

A big scientific problem is to govern the sensitivity of tumor
cells to radiation and chemotherapy. Almost all known compounds and
their combinations cause lesions of healthy tissues. Quite often,
toxic effects become noticeable before the antineoplastic effect.
They may be so severe that the patient has to be withdrawn from the
cure.

Experimental results demonstrate that MM waves do not affect
healthy cells and tissues. At the same time, they favor a more
rapid recovery of vital functions in affected tissues. When
combined with X rays or antineoplastic compounds, MM waves act as a
protector. This arises from an increased proliferative activity of
stem cells of the hematogenous system. As a result, mitotic
activity of karyocytes increases.

The effect of MM-wave radiation on the hematogenous system was
studied in animals with malignant tumors. The experiments were made
on 1,500 animals receiving X rays in combination with an
antineoplastic compoundcyclophosphane. It was found that MM-wave
radiation prolonged the life expectancy of the animals by 10 to 15
days, as compared to the control group.

Investigations of the combined influence of MM waves and X rays
were performed on primary tumors grafted into the CBA mice. It was
found that, when X-ray exposure was followed by MM-wave
irradiation, the tumor growth was retarded significantly. By the
thirtieth day, the tumor growth retardation reached 80% to 90%.
However, when X rays were applied alone or when MM-wave irradiation
preceded X-ray exposure, the tumor growth retardationdetermined by
the thirtieth daywas 60% to 65%. In this case, the karyocyte count
exhibited virtually no decrease: by the seventh day, it was at the
level of the physiological norm.

When X rays were applied alone, karyocytes exhibited a sluggish
recovery. Even by the seventh day, the karyocyte count failed to
reach the control level. When X-ray exposure was followed by
MM-wave irradiation, the karyocyte countmade by the seventh
dayreached the physiological norm.

Peripheral blood examination was also made during the experiments.
It revealed that animals subjected to MM-wave irradiation followed
by X-ray exposure exhibited greater erythrocyte and leukocyte
counts as compared to animals subjected either to X rays alone or
to X rays followed by MM waves.

A group subjected to the combined influence revealed a reduced
karyocyte count on the first day only, with the karyocyte
deficiency being 20%. By the fifth day, the karyocyte count reached
the physiological norm. After X-ray exposure, the karyocyte count
was recovered by the twenty-first day.

The sequential application of X rays and MM waves brought about a
significant tumor growth retardation. It was more pronounced than
that caused either by X-ray exposure alone or by MM-wave
irradiation followed by X-ray exposure. After a seven-day
irradiation, the tumor growth retardation reached 90% to 95%.
However, the karyocyte count remained decreased for 5 days. The
cell deficiency amounted to 30% within the first days. After that,
the karyocyte count exhibited gradual normalization. When the
double combination was applied, the tumor growth retardation
amounted to 90% by the thirtieth to thirty-fifth day.

Thus, the double combination not only counteracted the
hematogenous system damage, but it also retarded the tumor growth,
with both effects being stronger as compared to X rays alone.

Combined X rays and MM waves potentiated the effect of
cyclophosphane on the tumor within 13 days. The effect was greater
by a factor of 3 to 4 as compared to that without MM waves. The
peak of effect was observed by the twenty-fifth day.

The hematogenous system response was studied on a group of animals
subjected to the combined influence of cyclophosphane and MM waves.
By the third day, the karyocyte count of animals reached the
control level and retained it over the entire observation time (for
14 days). When the compound was employed alone, the karyocyte
countmade by the fourteenth daydid not reach the control
level.

The encouraging results of the first course of treatment suggested
that the treatment should continue. After the second course of
treatment, the antineoplastic effect became noticeable within 24
days. By the thirtieth day, the whole group of animals receiving
cyclophosphane was found dead, whereas all the animals receiving
the combined treatment were alive. The percent of tumor resolutions
reached 90% to 100%. These animals were followed up for 18 months,
with no relapses being observed. The time history of erythrocytes
was recorded for animals that received two courses of treatment. It
was found that the combined influence ensured the protection of
erythrocytes during the entire cure. In animals receiving combined
treatment, the erythrocyte countmade for 51 daysproved to be
normal.

Hence, the combined application of MM waves and cyclophosphane in
animals with sarcoma-180, on the one hand, decreases the compound
toxicity and, on the other hand, potentiates its effect on the
tumor.

In vitro experiments were made to study the effect of
low-intensity MM-waves on hemopoietic cells of the bone marrow[43]. With this end in view, L. P. Ignasheva and E. I. Soboleva
investigated the problem of survival of mice that had received a
lethal radiation dose. In their investigation, they transplanted a
cryogenically preserved bone marrow. After defrosting, they exposed
the bone marrow to MM waves.

Success for myelotransplantation depends on the preservation
quality of hemopoietic stem cells. Usually, bone marrow
sanguification recovers later in animals which underwent
transplantation using a defrosted bone marrow: it is delayed
by 7 to 8 days as compared to animals which underwent
transplantation using an extempore-produced bone marrow. It is
believed that quality of karyocytes is sufficient when animals that
had received a lethal radiation dose stay alive for more than 30
days.

Hybrid mice were used as donors and recipients. Cryogenically
preserved karyocytes were subjected to MM-wave irradiation at a
wavelength of 7.1 mm. Irradiation was carried out according to an
optimum program mode. Animals of the control group were not
performed transplantation. By the fifteenth day, they all died of
acute radiation sickness. The disease revealed typical clinical
manifestations: weight loss, adynamic motion, and receding
hair.

When a defrosted bone marrow was transplanted without MM-wave
irradiation, only 45% of animals survived by the thirtieth day.
When the defrosted bone marrow was subjected to MM-wave irradiation
before transplantation, 53% of recipients remained alive within the
observation time. The animals of both groups exhibited a slight
hypodynamia and an insignificant weight loss that showed tendency
towards recovery by the end of the observation time.

Hence, nonthermal low-intensity MM-wave irradiation produced a
beneficial effect on the stem cells of cryogenically preserved bone
marrow and increased the survival rate of post-myelotransplantation
recipients that had received a lethal radiation dose. The
above-described technique can be used to enhance the repopulation
ability of cryogenically preserved bone marrow.

Unorthodox experimental studies were made at the Institute for
Radio Engineering and Electronics of the Russian Academy of
Sciences in collaboration with the P. A. Gertsen Moscow Cancer
Research Institute. Launched in 1989 and 1990, these investigations
dealt with the interaction between malignant tumors and low-energy
nanosecond MM-wave and microwave pulses having a giant peak
powertens and hundreds of millions of watts [44, 45]. Despite a
giant radiation power, the heating of an object was virtually
absent because of a short pulse durationon the order of 10 ns. At
the same time, such short-pulse radiation was not ionizing, i. e.,
it did not cause bond scissions due to a very small quantum energy
in this spectral range. A distinguishing feature of such pulsed
radiation was a high intensity of the external alternating electric
fieldfrom 104 to 105 V cm1. This intensity is comparable with the
natural quasistatic intensity of an electric field in cell
membranes.

Investigations were performed on the Walker carcinosarcoma grafted
intramuscularly into the Wistar rats.

Multiple experiments were made using MM-wave and microwave
radiation with the above-mentioned parameters. They revealed that
exposed animals revealed a number of features, as compared to the
control ones. These features were as follows:

• life expectancy was prolonged after the
application of such waves;

• the growth rate of grafted tumors decreased
and stabilized (it was halted for several days);

• the tumor growth was halted, and the life
expectancy was much longer when MM waves or microwaves were
combined with chemotherapeutic compounds; and

• the metastasis degree profoundly decreased
both when MM waves and microwaves were used alone as well as when
they were combined with chemotherapeutic compounds.

In vitro experiments revealed that the tumor-cell count at
different destruction stages (up to their death) was greater in
exposed suspensions than in the nonexposed ones. A follow-up study
that lasted for 12 to 18 months revealed no noticeable changes in
the behavioral reactions and general state of exposed healthy
animals. A postmortem examination of exposed animals revealed no
pathologoanatomic changes in their liver, kidneys, adrenal glands,
and immunocompetent organs (such as the thymus, spleen, and
lymphatic nodes) as compared to the control animals of a
corresponding age. These investigations thus showed that pulsed
radiation has both direct and indirectthrough the immune system’s
activationeffects on tumor cells.

A research team headed by V. I. Govallo at the Central Research
Institute for Traumatology and Orthopedy in collaboration with the
“Istok” Research and Production Association conducted
investigations into the effect of MM waves on human lymphocytes and
fibroblasts [46]. It was demonstrated in vitro that human
lymphocytes and fibroblasts produce a factor-phytokine under MM
waves. It enhances the growth and functional activity of similar
cells. In high concentrations, phytokine is contained in destroyed
irradiated cells (lysates), and it is released in a cultural
medium. MM-wave irradiation itself does not stimulate cell growth,
does not change the expression of superficial lymphocyte receptors,
and does not have an effect on their sensitivity to mitogens or
exogenous immunomodulators. However, when added to a culture,
phytokine vigorously stimulates the proliferative potential of
lymphocytes and fibroblasts.

This factor-phytokine is produced in cytoplasm. It is bound up
with the activation of dehydrogenases: the concentration of
lactatedehydrogenase increases by a factor of 3 to 5 in irradiated
cells. This activation factor is attributed to a class of cell
regulatorscytokines. It does not belong to a group of interleukins
or interferons. However, it may be attributed to lymphokines or
monokines. This is a low-molecular glycosylation factor, secreted
locally or distantly. It acts in a paracrine or autocrine way, but
not in the endocrine one.

It is apparent that the described mechanism may underlie the
immunomodifying effect of MM-wave radiation. This effect was
observed while treating inpatients with suppurative diseases and
complications at the Central Research Institute for Traumatology
and Orthopedy. Difficulty in treatment of such diseases is
associated with a high severity of injuries, complicated and
long-term operations, insufficient immunologic reactivity of
patients, as well as with changes in the properties and behavior of
suppurative infections, which appear to be resistant to many
antibacterial agents.

MM waves were applied to treat severe missile and shotgun injuries
of the locomotor system. The injuries were complicated by
suppurative and wound infections. The results obtained are as
follows [47]:

• the duration of separate phases of the wound
process, including bad infected wounds, decreased by a factor of
1.5 to 2 as compared to the control group;

• MM waves produced a pronounced stimulating
effect on wound tissue regeneration (the daily fractional decrease
in the wound surface area virtually corresponded to that for
uncomplicated wounds);

• grafts revealed a 100% retention;

• the osteomyelitic process was eliminated: MM
waves relieved pain and subsided inflammation in the injured region
of a limb; they also stimulated total and local closing of fistulae
as well as epithelization of injured soft tissues;

• microbial semination of wounds was reduced
after opening and excision of festerous-necrotic foci.

Microbiological examinations were conducted in vitro to study the
effect of MM waves on microbes. It was found that MM waves produce
no direct effect on microbial susceptibility to antibiotics as well
as on their biochemical and cultural properties.

Investigations carried out demonstrated that MM waves normalize
immune-system parameters, which is of value for MM-wave therapy
efficiency. Patients who underwent serious reconstructive
operations suffer from secondary immunodeficiency, which
complicates their recovery. MM waves brought about pronounced
shifts in the patients’ immunograms. As a result, the patients
showed a fractional and absolute increase in T-lymphocyte and
T-helper counts (by 30 to 50% and 30 to 80%, respectively). The
patients also revealed an increased natural-killer count (by 40 to
60%).

Hence, instead of a direct antimicrobial effect on pathogenic
microflora, MM waves produce an indirect effect on it. They enhance
an organism’s general reactivity and increase wound-tissue
viability.

The immunostimulating effect of MM waves was clearly demonstrated
by a research team from Leningrad [48]. These researchers
investigated how MM-wave radiation protects against and prevents
from influenzal infections. To this end, animals received a lethal
dose of the influenza A virus. MM waves were applied to healthy
animals (preliminary irradiation) and to infected animals
(subsequent irradiation). It was found that they produced a
protective effect in both cases. The results obtained were as
follows:

• MM waves produced favorable therapeutic and
preventive effects on the survival rate and average life expectancy
in all experimental groups;

• the protection efficacy depends on the
irradiation procedure: the best protective effect (the death rate
was zero) was observed for a long-term preventive irradiation of
healthy animals before they were infected;

• the protective preventive effect was
potentiated when exposure time was extended to 7 to 17 days;
and

Besides experimental investigations, the researchers
retrospectively analyzed the epidemiological situation of
influenzal and acute respiratory viral infections in a group of
patients who underwent MM-wave therapy with respect to gastric
ulcer. The MM-wave course coincided with the epidemiological period
of influenza epidemy caused by the influenzavirus A. The group of
patients receiving MM-wave therapy was compared to the control
group (comparable by the age, health state, and conditions of
work). It was found that influenzal and acute-respiratory-disease
rates in the group of patients receiving MM-wave therapy were
smaller by a factor of 1.75 during the epidemy as compared to the
control group.

Inasmuch as many diseases cause secondary immunodeficiency, many
scientists pay special attention to the immunomodifying effect of
MM waves.

Gastric and duodenal ulcers, as well as many other diseases, are
caused by an imbalance between an organism’s aggression and its
protective factors. Immunity ranks first among protective factors.
In order to compare the efficiency of MM-wave therapy and
conventional treatment of ulcer, nonspecific immunity (phagocytosis
and lysozyme) and specific immunity (T lymphocytes, B lymphocytes,
IgA, IgM, and IgG) were examined [49]. Although the ulcer healed
over, the conventional pharmacotherapy did not enhance protective
factors. When MM waves were applied, the ulcer healed over without
a keloid scar. Furthermore, protective factors exhibited a
pronounced normalizing effect. In particular, this concerned
nonspecific and specific immunity. A dynamic observation of the
patients revealed that their protective factors were at a maximum 3
months after the cure termination. Since MM waves produced a
normalizing effect on an organism’s protective factors,
preventive MM-wave therapy was put forward.

When atopic dermatitis was treated using MM-wave therapy [50, 51],
the patients’ immune state was monitored using a number of
laboratory techniques. They were as follows: an active T-lymphocyte
count; total T-lymphocyte count; B-lymphocyte count; agar-gel
radial immunodiffusion for the IgA, IgM, and IgG counts of blood
serum; circulating-immune-complex (CIC) count of blood serum; as
well as immunoenzymic analysis of the total IgE and
allergen-specific IgE counts. Note, the allergen-specific IgE
includes antibodies against indoor, pollen, and food allergens. The
treatment performed favored the positive dynamics and stable
improvement of immunologic indices. This concerned both the
cellular immunity (such as rosette-forming cells) and the humoral
immunity (such as CIC, IgM, IgG, and IgE). Patients receiving
conventional therapy exhibited virtually no changes in cellular and
humoral immunity indices.

A research team [52] investigated the effect of MM waves on the
immune state of patients with sarcoidosis of lungs. Investigations
were made at the Central Research Institute for Tuberculosis of the
Russian Academy of Medical Sciences. The researchers counted T
lymphocytes and determined their functional and phagocytic
activity. They also counted B lymphocytes, immunoglobulins, as well
as CICs in blood serum (both before and after the treatment). The
application of MM waves gave rise to a universal stimulation of
functional activity of immunocompetent cells. They stimulated the
phagocytic activity of macrophages in the granulomatosis-stricken
region, in various lung regions, and in blood. Macrophage
activation facilitated the elimination of CICs from the body. They
were devoured by macrophages, and their content decreased in 87% to
91% of the patients after MM-wave therapy. This restored the blood
flow in lungs. As is known, when the CIC count of blood decreases,
it prevents microvessels of many organs from being damaged.

The last several years have seen a wide spread of herpesviruses.
This is associated with the absence of reliable prevention and drug
therapy insufficiency. Furthermore, the number of immunodeficiency
states is growing, which is caused by wide application of
antibacterial and hormonal compounds. The immune state was examined
when conventional treatment was combined with MM-wave therapy. The
examination involved counting T lymphocytes, B lymphocytes, CICs,
IgA, IgM, IgG, as well as studying the immune-response-modifier
tolerance. It was found that MM waves produced an immunostimulating
effect, which manifested itself in stimulated phagocytosis and
T-lymphocyte activity. This is of great importance for prevention
and treatment of diseases complicated by secondary immunodeficiency[53].

At present, urogenital inflammatory diseases are also widespread
in men and women. Most often, these diseases are caused by
chlamydias, mycoplasmas, and ureaplasmas. A distinguishing feature
of these microbes is their ability to cause stable
immunodeficiency. When antibiotic therapy is combined with
immunomodification, the recovery rate increases up to 70% (as
compared to 30% to 50% after conventional therapy) [54].

It is known that immunosuppression exacerbates acne.
Investigations were made of the effect of MM-wave therapy on the
cutaneous microbiocenosis in vulgaris-acne patients. All the
patients were recorded an immunogram showing cellular and humoral
immunity indices before and after the treatment. It was found that
conditionally pathogenic microbes did not grow on the skin of
patients whose immunologic indices were normalized by MM-wave
therapy. In these patients, clinical results were regarded as a
recovery or significant improvement. In general, the immunologic
indices of most patients exhibited positive dynamics, which was
accompanied by an improved state of skin microbiocenosis[55].

The central nervous system (CNS) is the main regulatory system. It
governs almost all processes occurring in a living being. Classical
investigations into electromagnetic biology revealed that the CNS
is the most sensitive system for electromagnetic fields [6, 56,
57]. Studies of the CNS role in the realization of biological
effects of low-intensity MM waves began at the earliest stage of
MM-wave therapy formation.

Professor Yu. A. Kholodov and Professor N. N. Lebedeva have been
heading experimental investigations at the Institute for Higher
Nerve Activity and Neurophysiology of the then-U.S.S.R. and
now-Russian Academy of Sciences since 1989. These investigations
deal with the sensory and subsensory (EEG) responses of healthy
human beings to peripheral stimuli of low-intensity MM-wave
radiation. Investigations of sensory responses, i. e.,
electromagnetic sensitivity of human beings [21, 5862] yielded a
number of interesting results. They are as follows:

• A human being reliably discerns MM-wave
signals from sham signals.

• Human sensitivity to MM waves depends both on
his or her individual features and on the biotropic parameters of
the field.

• MM-wave perception exhibits sensory asymmetry:
it is different for left and right hands.

An analysis of subjective feelings in human beings demonstrated
that a MM-wave stimulus “actuates” mechanoreceptors, nociceptors,
and free nerve endingsunmyelinated efferent fibers without
corpuscular structures at their ends. Evidently, we may ignore
fast-adapting mechanoreceptors because they discharge within 50 to
100 ms after sending an adequate stimulus. Nonspecific and weak
stimuli, such as low-intensity electromagnetic fields, can be
perceived by receptors that are slowly adapting or that have a
background activity (or when receptors combine these features). Of
mechanoreceptors, such features are inherent in Ruffinie’s endings,
tactile disks, and Merkel disks.

The nociceptors (pain receptors) of the skin are free nerve
endings with thin myelinated or unmyelinated nerve fibers. It was
hypothesized that nociceptors can perceive electromagnetic signals.
This hypothesis was based on a number of prerequisites. First, they
were found to exhibit polyspecificity to MM-wave stimuli. Second,
they revealed perception modality: pricking and burning, which are
regarded by experts as “prepain”. Third, electromagnetic
sensitivity disappeared in people whose exposure site was treated
with chloroethane that inactivated pain receptors [61]. Fourth,
clinical practitioners observed that, when electromagnetic
radiation was incident on a particular dermatome, it induced a
sensory response in the corresponding diseased organ. This may
arise from convergence of nociceptive efferent fibers from
dermatomes of internal organs to the same neurons of pain pathways.
This gives rise to skin hypersensitivity because visceral impulses
raise the excitation of intercalary neurons, which leads to
facilitation (relief).

An investigation was made of EEG responses of healthy subjects to
a long-term (30- to 60-min) peripheral MM-wave irradiation. It was
found that such irradiation produced changes in the spatiotemporal
organization of cerebral biopotentials. The alpha rhythm exhibited
a significant increase in its power in occipital cortical regions.
Furthermore, the theta rhythm revealed an average increase in its
coherence in central and frontal regions. Note, this increase was
more pronounced in the right brain, independent of exposure site
location [21].

The effect of EHF radiation on the CNS can also be evaluated by
studying behavioral reactions. For example, S. V. Khromova in her
Ph.D. thesis [64] demonstrated that EHF radiation can modify the
behavior-reflex activity of rats. This phenomenon manifested itself
both in the accelerated alteration of a developed conditioned food
reflex and in the delayed impairment of a conditioned defense
reflex.

Investigations of a stress-protective effect of MM waves were made
on animals at the State Research Center for Narcology, the Russian
Federation Ministry of Health. Such investigations were carried out
by Yu. L. Arzumanov with co-workers [65, 66]. The effect of MM-wave
radiation on the CNS was evaluated by special tests. They were
based on studying the inborn behavior that reflected various fields
of motivation-emotion activities. In the case of a conflict-defense
situation with stress, MM-wave radiation modified the behavior of
an experimental group of animals in such a way that it was
identical with the behavior of a passive control group.

A research team headed by Prof. N. A. Temur’yants achieved a
pronounced antistress effect of MM waves [67, 68]. In their
experiments, they studied the effect of MM-wave radiation on the
development of hypokinetic stress in rats. As distinct from control
animals, the experimental ones showed no decrease in the protective
functions of blood after a 9-day hypokinesia. Furthermore, they
revealed an increase in the examined indices (such as the
cytochemical state of neutrophiles and lymphocytes in peripheral
blood) as compared to the control animals. However, the efficiency
of antistress effect of MM waves depended on the individual
features of the higher nerve activity of rats. It was at a maximum
in rats with a low and medium moving activity.

It was also demonstrated that MM waves produce a modifying effect
on the functional CNS state in human beings under simulated stress
conditions [69]. This was proven by means of EEG
spectrum-correlation analysis, psychological test findings, as well
as cardiac-rhythm and exertion indices dynamics.

An investigation of the psychophysiological state of patients [70]
and development of new methods for inpatient psychoemotional
rehabilitation [71] revealed that MM-wave therapy relieves
situational and personal anxiety, improves memory, raises
attention, accelerates sensorimotor responses, as well as restores
and stabilizes the psychoemotional state of human beings.

It was also found that MM waves have an energizing effect. MM-wave
therapy was administered in combination with light therapy to
patients having a depressive symptomatology. These patients
suffered from maniac-depressive psychosis, cyclothymia,
schizophrenia, as well as vascular and involutional psychosis. It
was found that the combined treatment produced a favorable clinical
effect in 97% of the patients. A distinguishing feature of patients
who revealed a virtual recovery was a different degree of the
anxiety component in the depression structure, irrespective of its
nosological attribute. Furthermore, the vegetative nervous system
revealed hypersympathicotonic phenomena. An improvement was
observed when the vegetative nervous system had a mixed type and
when apathy predominated in the syndrome structure [72].

The results of tentative experimental and theoretical
investigations of biological effects of MM waves were summarized at
a special session of the General Physics and Astronomy Division of
the U.S.S.R. Academy of Sciences in 1973. This session was
initiated by Academician N. D. Devyatkov, and it was held in order
to familiarize the scientific community with unorthodox
MM-wave-induced biological effects.

The first attempt to explain the resonance pattern of the MM-wave
influence was made by V. I. Gaiduk and L. G. Koreneva in 1970 [73].
By way of example, they considered hemoglobin. They investigated
the effect of MM-wave radiation on distal histidine E7. It was
shown theoretically that distal histidine E7in engineering
mechanics, an analog for histidine is “a beam fixed at one end”has
an intrinsic resonance frequency, which falls within the EHF band.
Although this work had no continuation, the idea of a direct
resonance interaction between radiation and biological systems was
developed in other studies.

As far as 10 years ago, our concepts of biophysical mechanisms of
the interaction between low-intensity MM waves and biological
systems were reduced to basic ideas ensuing from the analysis of
biological effects enumerated in Section 2. In brief, they can be
described as follows. The primary reception of MM waves occurs in a
thin layer of an exposed surface. This is because all biological
objects contain water, which is the strongest MM-wave absorber. The
absorption mechanism is very simple. Water molecules possess a
great dipole momentapproximately 1.9 D, whereas their rotational
frequencies cover a wide range, the EHF band included. Hence, there
are ideal conditions for absorption of MM-wave radiation by water
molecules. The wave energy is converted into the kinetic energy of
water molecules: it is transformed mainly into the translational
degree of freedom. In addition, the wave energy is converted into
the rotational and librational degrees of freedom. By virtue of
molecule collisions, the acquired energy is rapidly thermalized.
The thermalization time is on the order of 1013 s. Apparently, it
is this energy thermalization that causes the convective motion of
liquid and gives rise to the capillary effect. Apart from that,
water molecules “heated” by EHF radiation produce an effect on
hydration of protein molecules. As a result, they change from a
functionally passive to functionally active state. After that, a
trigger mechanism may come into action. It initiates biochemical
reactions that are governed by protein molecules. Note, it is this
mechanism that may govern the synthesis of biologically active
substances (including the immunocompetent ones), produce an effect
on cell metabolism, stimulate the ATP synthesis, etc. It can be
hypothesized that MM waves are “embedded” in basic vital processes
according to this pattern.

Now, let us consider a key idea that was suggested by EHF-therapy
founders. The matter concerns the excitation of acoustoelectric
oscillations in plasma membranes. As was mentioned in Section 2,
coherent Frohlich oscillations and acoustoelectric membrane
oscillations evidently represent the same physical phenomenon.
However, it is infeasible to check this statement at present:
modern measuring equipment falls short of approximately five to
seven orders of sensitivity. Nevertheless, the idea of plasma
membrane oscillations is very fruitful by itself. Let us note that
it has been confirmed by other independent theoretical estimates.
They were obtained when the problem of electric stability of a
native plasma membrane was attacked. The membrane functions
normally under giant electric intensitieson the order of 105 V
cm1 (!). This issue is carefully considered in [33]. Note, pushing
off this fundamental idea, one can explain almost all known
experimental phenomena.

Completing our narration about the early formation of biophysical
mechanisms of the interaction of MM waves with biological systems,
we shall consider the problem of MM-wave perception by the entire
being. The matter concerns the role of the skin receptor system,
spinal cord, and CNS in the mechanisms of low-intensity MM-wave
identification in the presence of intrinsic noise. It is also
necessary to assess the significance of information carried by the
waves.

When such signals are perceived, a living being encounters two
problems. First, a mammal being (the human being included) has no
special-purpose system to perceive electromagnetic stimuli. Second,
low-intensity MM-wave radiation can be attributed to weak and
extremely weak influences. There are a few physical mechanisms that
enable biological systems to “receive” weak signals. Let us dwell
on some of them with due account of MM waves.

The key idea that biological objects can sense weak
electromagnetic fields is consistent with a hypothesis that MM
waves are “native” to biological objects and that biological
objects use these waves to govern their vital functions. As was
mentioned, this concept was proposed theoretically by a team of
Russian scientists headed by N. D. Devyatkov in the mid 1960s.
Thereafter, this hypothesis received an indirect theoretical
corroboration in an independent study made by a prominent German
physicistH. Frohlich.

Electric dipoles of a plasma membrane generate narrow-band
electromagnetic waves whose power is about 1023 W. Hence, living
cells should be sensitive to such a small power. Furthermore,
according to the reciprocity principle, cells should be sensitive
to external radiation that has such a power. The effect of
amplification of weak external electromagnetic fields may take
place immediately in the skin [74]. A volt-ampere dependence of
slit contacts has a domain with negative differential conductivity.
The existence of this domain is a sufficient and necessary
condition for realization of input signal amplification. Especially
large gain factorson the order of 30 to 60 dB by powercan be
achieved by means of regenerative and superregenerative
amplification.

The authors of [76] discussed a new physical mechanism of high
sensitivity of water-containing biological objects to weak
electromagnetic fields (on the order of units of microwatts). This
mechanism is based on the generation of intrinsic resonance
frequencies by water clusters. These frequencies were discovered by
Saratov physicists. They fall within a frequency range from about
50 to 70 GHz. When biological objects are exposed to weak
electromagnetic waves at these frequencies, their water-molecule
oscillators lock on to the external signal frequency and amplify
the signal by means of synchronized oscillation or regenerative
amplification. Waves at these frequencies pass through aqueous
media almost without losslike the Davydov soliton waves [77]. As a
result, they penetrate deeply into an exposed object and involve
deep structures in the interaction process.

Another approach was also taken to explain the sensitivity of
biological objects to weak electromagnetic fields. It is based on
the “water memory” phenomenon [78]. The essence of this phenomenon
is as follows. It is known that liquid water is structured and that
it consists mainly of clusters, with water molecules being bound to
each other by hydrogen bonds. It was found that a hydrogen atom
that is located between the two nearest oxygen atoms can take up
one of two positions: near either of the oxygen atoms. One of the
positions is stable, whereas the other is not. The energy of
hydrogen-atom transition from the stable to unstable state
corresponds to that of an EHF quantum. As a result, hydrogen atoms
may change to unstable states under EHF radiation. They may
thereafter return to their stable states with inevitable reemission
of EHF quanta (“water memory”). Hence, water acts as a
low-intensity molecular oscillator of electromagnetic waves in the
EHF band. As was shown in [79], water molecules may stay in the
unstable state for a long timeon the order of several weeks.

A physical phenomenon that was discovered 20 years ago, or
thereabouts, provided new and unexpected explanations of the
mechanism of the effect of weak signals on biological systems. This
physical phenomenon was called stochastic resonance, or stochastic
filtration in radio engineering. The most complete information
about the stochastic resonance and about its possible applications,
including biology and medicine, is presented in an unorthodox
review [80]. In the early 1980s, researchers discovered that the
presence of noise sources in nonlinear dynamic systems can provide
such operation modes of the systems that are new in principle.
These operation modes cannot be realized in the absence of noise.
Noise was demonstrated to play a “favorable” role in nonlinear
systems by means of enhancing the motion order strength in the
systems. Furthermore, it was shown to improve system performance,
for example, “to form more regular structures, to increase the
coherence degree, to raise the gain factor, and to increase the
signal-to-noise ratio” [80]. Let us remember that according to the
generally accepted, classical, point of view, specialists always
regarded the presence of noise as a negative factor. Noise always
had to impair the behavior of dynamic systems, and it always had to
be “controlled.” “Stochastic resonance specifies a group of
phenomena such that a nonlinear system’s response to a weak
external signal increases considerably with an increase in noise
intensity. Furthermore, the effect shows a maximum at some optimum
noise level” [80].

Numerous experimental studies were afterward performed on various
physical objects. The results obtained made it possible to draw a
principal conclusion: stochastic resonance is a fundamental
physical phenomenon that was unknown earlier; it is observable in
nonlinear dynamic systems and makes it possible to control their
main parameters. Note, stochastic resonance can also take place in
nondynamic or threshold systems. It can be realized in the presence
of external noise or in the presence of internal noise of an
investigated system. This is of special interest for biological
systems, which meet the requirements for stochastic
resonance.

A more sophisticated problem is to investigate and comprehend the
physiological mechanisms of biological and therapeutic effects of
low-intensity MM-waves at the level of an entire organism. This is
owing to the fact that the investigated objectthe human beingis a
very complex biological system. It possesses myriad positive and
negative feedback loops and regulation levels [81]. To begin with,
one needs to analyze the primary physiological targets present in
the MM-wave exposure site. As is known, MM waves penetrate into the
human skin at a depth of 300 to 500 m. In other words, they are
absorbed almost completely in the epidermis and the top dermis.
Hence, MM waves directly influence CNS receptors (such as
mechanoreceptors, nociceptors, and free nerve endings), APUD cells
(such as the diffuse neuroendocrine cells, mastocytes, and Merkel
cells), and immune cells (such as the T-lymphocyte skin pool). In
addition, these waves produce a direct effect on the microcapillary
bed and biologically active points.

It is apparent that these five primary physiological targets are
the five “entry” gates. They determine the involvement of
corresponding systems in realization of biological and therapeutic
effects of MM-wave radiation. The latter acts on every basic
regulation systems of an organism as a peculiar triggering factor.
This has been confirmed by many clinical investigations. The direct
and simultaneous “triggering” of the aforementioned systems
initiates a complex mediate influence on other organs and systems
(such as the hematogenous, humoral, vegetative nervous systems). As
a result, a MM-wave-induced reaction involves the entire being. The
features of this reaction depend both on the biotropic parameters
of the MM-wave stimulus and on the functional state of the human
being. MM-wave radiation produces both nonspecific and specific
effects. The latter include wound healing, injury sanitation,
tissue regeneration, pain relief, itch mitigation, hyperemia
elimination, etc.

At present, a nonspecific effect is regarded as a reaction of
enhanced nonspecific resistivity of an organism. In turn, this
initiates adapting and antistress reactions of higher reactivity
levels [82].

A promising approach was also developed in [83]. The authors of
that work made an attempt to create a unified concept. To this end,
the entire being’s response to low-intensity MM waves was bound up
with some principal elements of pattern-recognition theory. The
authors did it with respect to the problem of neurocomputing. The
key notions of this concept are autodiagnostics (when MM waves
begin to interact with an organism) and autotherapy (when an
organism uses autodiagnostic findings to begin the production of
medicinal agents). These functions are realized with the aid of
lamellar formations of the spinal cord (the Rexed lamellae). They
preprocess and identify information about the external stimulus (MM
waves). Hence, these formations act as a peculiar neurocomputer
that prepares specific information to actuate systems that govern
and maintain bodily homeostasis.

5. Application of Low-intensity MM-wave Radiation in
Medicine

In the early 1970s, Academician N. D. Devyatkov initiated a
program of clinical evaluation of MM waves in respect of treating
various diseases. This program was approved by the U.S.S.R. and
R.S.F.S.R. Ministries of Health and was executed in a number of
medical establishments. The MM-wave technique was tested in more
than 60 clinics, including large medical centers, such as the
All-Union Cancer Research Center of the Russian Academy of Medical
Sciences, the Central Research Institute for Traumatology and
Orthopedy of the Russian Federation Ministry of Health, the P. A.
Hertsen Moscow Cancer Research Institute, as well as clinics
affiliated with the State Medical University, Moscow Medical
Academy, and Moscow State Institute for Dentistry. The results
obtained provided evidence for high efficiency of MM-wave therapy
for the following diseases: cardiovascular (stable and unstable
stenocardia, hypertonia, and myocardial infarction), neurological
(pain syndromes, neuritis, radiculitis, and osteochondrosis),
urological (pyelonephritis, impotence, and prostatitis),
gynecological (adnexitis, endometritis, and uterine neck erosions),
dermatological (neurodermite, including psoriasis, streptoderma,
and acne), gastroenterological (gastric ulcer, duodenal ulcer,
hepatitis, and cholecystopancreatitis), stomatological
(periodontosis, periodontitis, some types of stomatitis, and
periostitis), as well as oncological (to protect the hematogenous
system and to remove side effects of chemotherapy).

The experience of applying MM waves in clinical practice revealed
no ultimate side effects. MM-wave therapy went well with other
therapeutic techniques (such as pharmacotherapy, physiotherapy,
etc.). Furthermore, it exhibited no absolute contraindications. As
distinct from drug therapy, MM-wave therapy had no side
effects.

MM-wave therapy reveals some features such as noninvasiveness,
polytherapeutic effect, monotherapeutic effect, antistress effect,
immunomodifying effect, and painkilling effect. Currently,
low-intensity MM-wave radiation (MM-wave therapy) finds wide
application in medicine. It is employed both to treat and prevent a
wide gamut of maladies.

Cardiovascular diseases are among the most urgent problems of
present-day medicine. The ischemic disease of the heart is among
the most widespread cardiovascular pathologies. The death rate of
this illness ranks high worldwide.

The first report on the application of electromagnetic MM waves in
treatment of cardiovascular diseases came to light as far back as
1980. Over the years passed by, researchers have acquired broad
experience in using MM waves to treat heart ischemia and hypertonia[8488]. It was demonstrated that MM-wave therapy produced a
clinical effect, which was verified by laboratory and instrumental
findings. Apart from that, researchers developed techniques for
individual selection of MM-wave treatment. It was shown that
MM-wave therapy can substantially reduce the dose of antianginal
compounds. Moreover, a nitrate therapy was stopped completely in
patients having exertion stenocardia of the first and second
functional classes. In such patients, MM-wave therapy proved to be
most effective in treating both painful and painless myocardial
ischemia.

The most severe patients had exertion stenocardia of the third and
fourth functional classes and rest stenocardia complicated by one
or several stenotic coronary arteries. Although these patients
received great doses of nitrates, beta adrenoblockers, calcium
antagonists, and disaggregants, the treatment appeared ineffective.
By the end of a MM-wave therapy course, 80% of the patients
revealed a positive clinical effect. The application of MM waves
reduced the number of episodes of painful and painless myocardial
ischemia. Hence, MM-wave therapy produced both painkilling and
antianginal effects.

Unstable stenocardia is classified among acute ischemic diseases
of the heart. It is especially dangerous in the case of an abrupt
onset (within a few days) or intensifying anginal attacks. Unstable
stenocardia may take a bad course, resulting in myocardial
infarction, sudden death, or chronic stenocardia. The clinical
application of MM-wave therapy was found to be effective in 60% of
the cases. The treatment was successful even when MM waves were
used as a monotherapy. Being combined with pharmacotherapy, MM-wave
therapy increased the rate of positive clinical effects. The
conducted therapy produced favorable effects in every patient of
the examined group. According to literature findings, myocardial
infarction develops in 12% to 20% of patients having unstable
stenocardia. However, after MM-wave therapy, myocardial infarction
developed in none of the patients with unstable stenocardia. Thus,
the involvement of MM-wave therapy in the combined treatment of
unstable stenocardia decreased the risk of myocardial
infarction.

Myocardial infarction is the most severe ischemic disease of the
heart. At the acute stage, it is most dangerous for the patient to
develop such complications as a cardiac-rhythm disorder or acute
left ventricular failure. Serious postinfarction complications
include the development of chronic circulatory deficiency and early
postinfarction stenocardia. When MM-wave therapy was administered
within the first hours of myocardial infarction and its
complications, it decreased the number of episodes of acute left
ventricular failure. It also decreased the rate of postinfarction
stenocardia and chronic circulatory deficiency. Furthermore,
MM-wave therapy substantially increased the Garkavi-Kvakina-Ukolova
index [82]. It is known that myocardial infarction shocks a person.
Shock reactions worsen the disease course. This forms a vicious
pathogenic circle. It was shown that patients with an acute stress
reaction revealed a greater leukocyte count and a longer pain
syndrome. Such patients exhibit the greatest death rate. Before
treatment, stress reactions were obderved in 55.6% of patients,
whereas calm activation reactions were found in 21.0% of patients.
After a course of treatment, stress reactions decreased down to
11.1%. Calm activation reactions and training reactions were
observed in 50.4% and 34.2%, respectively. Patients retaining
stress reactions develop postinfarction stenocardia more often (as
compared to those with reactions of other types). It was also found
that patients who received MM-wave therapy revealed a raised degree
of antioxidant protection. They exhibited a decrease in the malonic
dialdehyde content. This substance is among the products of
peroxide oxidation of lipids. It was also established that drug
treatment caused no decrease in this index (Table 1).

The superoxide-dismutase (SOD) enzyme is an important component of
antioxidant protection. According to present-day views, when the
SOD activity decreases below 50% of the norm, the concentration of
superoxide anion radicals shows an uncontrolled increase. This may
cause irreversible changes in cells and tissues. MM-wave therapy
enhances the activity of this enzyme, which increases the degree of
cell protection. These changes take place in blood plasma and
thrombocytes (Table 2).

The deposition of immune complexes on the arterial wall may cause
atherosclerosis. The liberation of vasoactive amines under the
action of immune complexes increases the vascular wall permeation.
This promotes the penetration of immune complexes into tissues, the
arterial wall included. The interaction between immune complexes
and thrombocytes enhances the activation and adhesion of
thrombocytes, which may cause thrombus formation.

MM-wave therapy was found to significantly decrease the CIC count
of blood plasma in patients with cardiac ischemia. This phenomenon
was not observed in the control group. This means that conventional
drug therapy has no effect on the pathogenic aspect of cardiac
ischemia. The complimentary activity of serum was found to
decrease. This can be associated with a sluggish stimulation of the
compliment by immune complexes. Hence, MM-wave therapy makes it
possible to correct for immunologic disorders in patients with
cardiac ischemia. This can be of value not only for treating this
nosology, but also for treating the atherogenic process on the
whole.

Microcirculatory disorders are a serious element of cardiovascular
pathologies. Tissue perfusion can be impaired not only in the case
of atherosclerosis of main vessels but also in the case of
microcirculatory blocking. The latter is caused by microscopic
thrombi and inelastic erythrocytes.

Investigations were made of microcirculation in the bulbar
conjunctiva of patients with cardiac ischemia who received MM-wave
therapy. It was found that the MM-wave therapy produced a
significant decrease in the total conjunctival index as well as in
the index of vascular and intravascular changes. It also enlarged
the arteriole caliber, increased the number of functioning limbic
ansae, and decreased the content of erythrocyte aggregants in
venules. The cerebral blood circulation was estimated in hypertonic
patients administered to MM-wave therapy. This was done with the
aid of dynamic scintigraphy of cerebral circulation using
99mTechnetium labeled compounds. The results obtained revealed
blood flow improvement in affected arteries and improved blood
circulation in ischemia-stricken regions.

According to the World Health Organization, the death rate of
cancer ranks second to the cardiovascular one.

Clinical evaluation of low-intensity MM-wave radiation and
development of therapeutic techniques for cancer treatment have
been carried out since 1980. These investigations were pursued at
the P. A. Gertsen Moscow Cancer Research Institute [44]. They were
made in patients with mammary cancer. First, this disease is
widespread, and, second, this pathology is often treated using
radiotherapy and antineoplastic pharmaceuticals. Such treatment
causes changes in human vital functions. The studies were made in
patients having mammary cancer of the II-b and III-b stages who
received chemotherapy and radiotherapy. The structural and
functional state of blood cells was examined before treatment,
after three MM-wave irradiation sessions, in the middle of the
cure, and after its termination. The human general state was
assessed by subjective data, symptomatology, and adapting
reactions. The type of such reactions was determined from
lymphocyte percentage, leukocyte formula, and the ratio of
leukocytes to segmented neutrophiles.

Chemotherapeutic compounds were introduced before surgical
excision according to the following scheme: 3 g of fluoruracil, 2.8
g of cyclophosphane, and 60 mg of methotrexate.

Before antineoplastic pharmacotherapy, patients were subjected to
a 3-day MM-wave irradiation: 60-min daily sessions. During
chemotherapy, irradiation was performed 1 h before the introduction
of antineoplastic compounds. When a chemotherapy course was
finished, MM-wave irradiation was administered for the next 3 days.
Usually, a course of MM-wave therapy consisted of 14 to 15
sessions. This cure was administered to 343 patients. A control
group embraced 339 patients who received chemotherapy according to
the above-described scheme. When the combined treatment was
finished completely, 95.1% of the patients exhibited a satisfactory
general state (without blood-circulation stimulants). When the
chemotherapy course (without MM-wave irradiation) was finished,
74.2% of patients revealed an unsatisfactory general state as well
as a reduced leukocyte count of blood. This occurred in spite of
the fact that the patients received blood transfusion and
blood-circulation stimulants. This regularity persisted during
subsequent (adjuvant) chemotherapy courses. In the first year of
treatment, adjuvant chemotherapy was administered every three
months (not more than three courses). In the second year of
treatment, it was administered twice at an interval of 5
months.

The ability of MM waves to normalize the leukocyte count was
investigated in patients with leukopenia. The investigation was
made in 900 patients whose initial leukocyte count of blood was
less than 3,000 (from 2,300 to 2,700). A course of treatment lasted
for 12 days. The sessions were administered daily. After the cure,
the leukocyte count of blood was normalized in 80% of the patients.
This allowed the patients to undergo a complete course of
chemotherapy.

The bone marrow was examined in patients taking antineoplastic
compounds and receiving MM-wave therapy. The results obtained
demonstrated that MM-wave therapy initially ejected reserved blood
from blood pools. It increased the total volume of circulating
blood, which improved oxygen exchange. This might result in a
better tolerance to antineoplastic compounds and reduced side toxic
effects. The proliferative activity of the bone marrow was found to
grow 4 to 5 days after the MM-wave therapy commencement.

Hence, the clinical findings show that MM waves allow cancer
patients to undergo a complete course of chemotherapy without a
significant decrease in their blood indices and without
blood-circulation stimulants.

Melanoma is a highly malignant tumor of the skin. It spreads to
other parts of the body via the bloodstream or the lymphatic
channels. The rate of this disease has increased over the last
several owing to environmental pollution. Surgical excision is
common for treating melanomas. When melanoma has metastases, it is
regarded incurable: a five-year survival remains very rare.
According to Russian and foreign scientists, the survival rate
constitutes 75% at the first clinical stage, 32% at the second one,
and 0% at the third one. Skin melanoma metastases occur in 20% to
25% of primarily treated patients within 6 to 18 months. When the
process has spread, chemotherapy is used. However, melanoma remains
resistant to antineoplastic compounds. Adjuvant chemotherapy
courses following surgical excision postpone neither metastasis
development nor tumor relapses. MM-wave radiation was employed to
prevent relapses and metastases in patients with primary melanoma
of the skin after surgical treatment. The clinical experience
gained demonstrated a beneficial effect of MM waves. The first
course of treatment consisted of 10 daily sessions lasting for 60
min. The MM-wave irradiation sessions were performed immediately
after surgical intervention. The second course was administered 1
month after the first one terminated. The third course was
performed 3 months after the second, whereas the fourth course was
conducted 6 months after the third. Dynamic observation lasted for
9 to 18 months. None of the patients revealed relapses or
metastases. Apparently, MM-wave irradiation stimulated the immune
system and thus enhanced the individual’s natural antineoplastic
protection.

Apart from that, scientists of the P. A. Gertsen Moscow Cancer
Research Institute studied the effect of MM-wave radiation on the
course of wound processes. The investigations were performed in
1,302 patients having both sutured and open wounds (after laser
tumor excision). The experimental and control group consisted of
651 patients. The wound process was evaluated by the degree of
inflammation, necrosis, and granulation, as well as by the terms of
granulation, epithelization, and healing. A course of treatment
comprised 15 daily sessions lasting for 60 min. In the case of open
superficial wounds, the device’s horn was positioned on the skin at
a distance of 2 to 2.5 cm from the wound. When operations were
performed on the abdominal cavity and thorax, the horn was
positioned on the sternum. The results obtained revealed that
MM-wave radiation produced a favorable effect on wound healing. The
patients noted pain and discomfort alleviation in the wound. At the
first stage of wound process (when tissue alteration is most
pronounced), MM-wave irradiation suppressed necrosis and perifocal
inflammation. When vascular reactions (such as edema and hyperemia)
predominated, MM-wave irradiation eliminated them 3 to 5 days after
the treatment commencement. In the control, these reactions
persisted for not less than 8 days. An antiphlogistic effect of
MM-wave radiation was most pronounced in patients with sutured
wounds. None of the patients subjected to MM-wave irradiation
revealed the opening of sutures, whereas 9% of patients of the
control group did not hold their sutures. Presumably, MM waves
recovered microcirculation and effective receptors, which
normalized wound healing autoregulation. It is significant that
MM-wave-based wound healing did not result in ugly scars or
keloids. This is of special importance for facial treatment.

When MM-wave radiation was used to heal open wounds, the following
results were obtained. Granules revealed an early maturationon the
third to fifth day. Wounds revealed overall mature granulation (as
distinct from nonlaser wounds that exhibit insular granulation).
Overall mature granulation expedited wound closure by 5 to 7 days.
Granulation overgrowth was not observed. MM-wave radiation
facilitated wound epithelization. It started uniformly at wound
edges. This resulted in the concentric contraction of wound edges
and skin regeneration. A daily growth of epithelium reached 2
to 3 mm. So, MM-wave radiation gave rise to optimum wound healing,
which curtailed the healing by 3 to 5 days.

The clinical studies of MM waves applied in traumatology and
orthopedy were launched at the N. N. Priorov Central Research
Institute for Traumatology and Orthopedy. Since 1987, this
technique has been used there in thousands of patients with various
bone-muscular pathologies. The latter include serious shotgun
wounds of limbs, which are often encountered in the Russian
Federation. Between 1987 and 1990, this technique was used to treat
severe war pathologies of the locomotor system under extreme
conditions. MM-wave therapy was approved by the Central Military
Hospital of the Defense Ministry of the Afghanistan Republic (the
N. N. Priorov Central Institute for Traumatology and Orthopedy had
direct scientific contacts with this hospital during that time).
MM-wave therapy was also applied to the victims of the Armenian
earthquake, various natural disasters, and diverse catastrophes.
They were also treated at the N. N. Priorov Central Institute for
Traumatology and Orthopedy [8992]. Cytological examinations were
conducted to demonstrate that the therapeutic effect of MM waves
may result from the enhanced proliferative potential of exposed
cells. The action of MM waves stimulates the synthesis of
cytotoxins in cytoplasm. Cytotoxins produce an effect that is
similar to the growth factor. Although cytotoxins are accumulated
in cytoplasm, they can be secreted out. As a result, they can
produce both contact and distant effects. It seems that the
stimulating effect of MM waves on cell growth is not restricted to
cutaneous fibroblasts and blood lymphocytes. Evidently, this effect
has a universal character and involves cells of various tissue
architectures.

When treating orthopedic and traumatic patients, MM waves should
produce an effect on cellular growth regulation and
cytodifferentiation. This is essential to stimulate reparation
processes in the affected region. MM-wave therapy acts as a
biological component of the complex therapy. The latter is targeted
at the recovery of functional capabilities of tissue structures
that are either affected by or involved in the bone-muscular
pathology.

Over the last decade, EHF therapy has been firmly established as
one of the most effective methods of conservative treatment of
orthopedic, traumatic, and surgical patients. The application of
EHF therapy at the N. N. Priorov Central Institute for Traumatology
and Orthopedy yielded broad experience of using MM waves in the
complex treatment of patients with trophic and tissue-viability
disorders (typical of shotgun wounds). It can be stated that MM
waves provide a new quality of treatment, which overcomes the
previous problems of medical rehabilitation of such patients. This
is confirmed by an analysis of the results of using EHF therapy for
different bone-muscular pathologies complicated by impaired tissue
trophics and inhibited reparation processes in the affected
region.

An investigation was made of applying EHF therapy to patients with
neurodystrophic changes in tissue trophics. These changes were
caused by shotgun wounds of limbs. Clinically, these patients
revealed persistently aggravating suppurative-necrotic processes in
their amputation stumps. The results of MM-wave treatment are
listed in Tables 3 and 4.

The normalizing effect of MM-wave therapy on wound healing was
also confirmed by the time history of adapting reactions. Before
MM-wave treatment, an absolute majority of patients (91.8%)
revealed a stress reaction that was prognostically unfavorable.
Under the action of MM-wave therapy, they changed their type of
adapting reactions. This resulted from a sharp decrease in the
number of patients with stress reactions (13.5%) as well as from a
simultaneous increase in the number of patients with raised (59.5%)
and calm (24.3%) activation. These findings were evidence that MM
waves can produce a beneficial effect on neurodystrophic processes.
This improves tissue trophics and viability in the affected
region.

MM-wave therapy was also found to be highly effective in treating
chronic (shotgun and traumatic) osteomyelitis and pressure sores.
It was also demonstrated both to decrease the microbial semination
of wounds and to facilitate the jointing of bone fractures.

MM-wave therapy efficiency was investigated at the Central
Research Institute for Tuberculosis. To this end, patients with
various forms of pulmonary tuberculosis received a basic course of
chemotherapy using 3 or 4 tuberculostatic compounds (such as
isoniazid, rifampin, pyrazinamide, and kanamycin). At different
stages, basic chemotherapy was combined with a course of MM-wave
therapy. Experimental and clinical studies revealed that
low-intensity MM waves produced a normalizing effect on many
clinical parameters, such as the formed elements of blood and blood
plasma proteins. In addition, MM waves stimulated lymphocyte
proliferation in immunogenic organs. As a result, macrophages
present in the bone marrow actively invaded tuberculosis-stricken
organs (mainly, the lungs) to normalized external respiration and
regional circulation in them. Additionally, macrophages favored the
homeostasis recovery during chronic infections, such as
tuberculosis [52].

MM-wave therapy was also employed in the complex treatment of
sarcoidosis of lungs and intrathoracic lymph nodes. After a course
of treatment (20 sessions), the patients were subjected to X-ray
examination. It revealed a noticeable resolution of
parenchymal-interstitial infiltration, disappearance of granuloma
shadows, as well as reduction of alveolitis symptoms, interstitial
edema, and pleural reactions. The size of intrathoracic lymph nodes
decreased by half. The phagocyte function of macrophages was
substantially activated in granuloma-stricken regions, separate
lung regions, and blood. In other words, the functional activity of
immunocompetent cells was universal. It is significant that MM-wave
therapy reduced the dose of corticosteroid compounds: they were
taken at a dose of 10 to 15 mg every other day. Moreover,
corticosteroid compounds were completely cancelled in half of
patients with firstly-diagnosed carcoidosis.

Gastric and duodenal ulcers are among widespread digestive
diseases. Ulcer strikes 7% to 10% of adult population in developed
countries. The last several years have shown tendency to increase
the number of primarily diagnosed ulcers, especially in young
people.

At present, ulcer is widely treated using complex pharmacotherapy.
The latter is targeted at different pathogenic mechanisms of the
disease. However, pharmacotherapy is not very effective: chronic
ulcers heal over for a long time, therapeutic results are unstable,
and 30 to 40% of the patients are resistant to the treatment. When
patients simultaneously take up to 3 drugs, 18% of them may exhibit
side effects. A simultaneous intake of 5 to 6 drugs may cause side
effects in 81% of the patients. This is because many drug compounds
suffer from various toxic side effects and may cause
allergies.

MM-wave therapy efficiency was assessed in more than 3,000
patients with ulcer (experimental group). The results obtained were
compared to those obtained for drug-treated patients (control
group). These patients received a traditional complex of drug
compounds (such as antacids, spasmolytics, secretion inhibitors,
and reparants).

Ulcers healed over in 98.6% of patients of the experimental group
and in 82% of patients of the control group. The healing lasted for
21.11.4 days in the experimental group and for 37.51.9 days in
the control group. Note, duodenal ulcers healed over faster than
gastric ulcers in both groups. For example, the healing of duodenal
ulcer lasted for 17.61.2 days in the experimental group and for
35.82.0 days in the control group, whereas the healing of gastric
ulcer lasted for 28.12.1 days in the experimental group and for
45.15.3 days in the control one.

Patients who underwent MM-wave therapy were subjected to a
follow-up study. To this end, a dynamic endoscopic examination was
made 3 to 4 months after the treatment. Relapses were revealed in
51% of patients of the experimental group and in 82% of patients of
the control group. MM-wave therapy increased the level of
antioxidant activity and normalized the rheological properties of
blood. For example, it decreased blood viscosity, packed cell
volume, and erythrocyte deformability index. It is also significant
that patients with erythrocyte aggregation exhibited a decreased
aggregation rate, and conversely, patients without erythrocyte
aggregation revealed a raised aggregation rate. In addition,
MM-wave therapy normalized phagocytosis [49].

Unfortunately, the limited space of this publication disallows us
to tell the reader about all MM-wave therapy capabilities. Clinical
studies have reliably verified the high efficiency of this
technique with respect to more than 120 nosologic forms (and this
number is becoming larger). Evidently, MM-wave therapy is a method
about which ancient physicians used to dream: it “treats a person,
not a disease.”

Conclusions

Summarizing the results of the 30-year study of biological
effects of low-intensity MM waves, we may ascertain the following.
As it often happens, applied research and commercialization have
outdistanced fundamental investigations.

The wide application of MM waves in medicine, biotechnology,
animal husbandry, and plant cultivation has taken a giant step
forward. By this time, Russia has manufactured more than 10,000
MM-wave therapy devices, organized more than 2,500 MM-wave therapy
rooms, and treated over 2,500,000 patients.

Since 1992, twenty-seven volumes of the Journal on Millimeter
Waves in Biology and Medicine (Millimetrovye Volny v Biologii i
Meditsine) have been published as well as 12 symposia on Millimeter
Waves in Biology and Medicine and 11 workshops have been
held.

During this time, we have issued 13 volumes of symposium and
workshop proceedings, 4 monographs, 3 popular scientific brochures,
and more than 2,600 articles. Furthermore, our scientific
attainments have been protected by 22 Russian Federation patents.
In the year 2000, we were awarded the Russian Federation State
Prize in Science and Technology for our research in this field of
science.

However, scientists-biophysicists,
physiologists, and physicianscarry on their further scientific
investigations into the mechanism of biological effects. By now,
they have approached a more complete understanding of the role of
low-intensity MM-wave radiation in the vital processes of
biological systems at different organization levels.

December, 2015

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